Supporting data for "PeptideMiner – Neuropeptide Discovery across the Animal Kingdom"

Neuropeptides are the largest and most diverse class of cell-to-cell signaling molecules, holding important roles in animal physiology and behavior. They are evolutionarily ancient and ubiquitously present across the animal kingdom. Over 200 human neuropeptides are known, yet only a handful are well understood. A recognized bottleneck is the lack of probes to study their function and therapeutic potential. Neuropeptide homologs are also observed in animal venoms, where they can facilitate prey capture or defensive strategies. Mapping neuropeptide families across the animal kingdom is challenging due to their high sequence divergence and short mature peptide sequences. Therefore, we developed PeptideMiner, a search tool that employs profile-hidden Markov models that allow family-specific peptide discovery. PeptideMiner was systematically validated and benchmarked to existing methods, demonstrating its efficiency. Applying PeptideMiner to venom transcriptomes, we discovered 10 novel natriuretic peptide sequences from evolutionarily distant organisms and 57 novel insulin-like sequences from marine predatory cone snails. Chemical synthesis followed by structure-activity relationship studies of newly identified conoinsulins at the human insulin receptors emphasizes the value of this approach in providing new insights into ligand-receptor interactions and identifying new pharmacological probes and therapeutic leads. PeptideMiner is a powerful tool for discovering new bioactive peptides and family-specific homologs, accelerating natural product discovery and evolutionary analyses.